There are unprecedented opportunities to exploit the information emerging from the Human and Mouse Genome Projects, as well as the HapMap project, for assessment of individual susceptibility to common diseases such as cancer, diabetes, obesity, or cardiovascular disorders. Identification of individuals at risk will have major implications for prevention as well as treatment of these conditions, and will have a fundamental impact on approaches to health care. At present, in spite of the general agreement that "personalized medicine" is a major goal of the NIH, there is as yet no consensus regarding the methods and approaches that should be used to achieve this goal. UCSF is one of the foremost medical centers in the US, with an extremely large patient population and vast experience in the treatment of human disease. UCSF also has in depth experience in the development of mouse models of human disease, in particular cancer, cardiovascular and immunodeficiency. We therefore have a unique opportunity to exploit the patient and tissue resources, as well as the mouse models available across the campus by carrying out large scale genome-wide and targeted genotyping studies of DNA samples from appropriate patients and controls. This proposal is for the purchase of the Sequenom MassArray genotyping System for the analysis of DNA samples from patients and controls. Although much attention has recently been focused on approaches to high throughput whole genome scanning, there is a major requirement for a targeted approach that allows low-medium throughput analysis of specific candidate genes and SNPs. While the Affymetrix and Illumina systems are well suited to simultaneous analysis of large numbers of SNPs, the Sequenom system is most appropriate for low-intermediate SNP numbers that can be typed rapidly on large numbers of patient samples. At the moment, there is no cost -effective SNP genotyping service of this kind available on the campus. The projects that are planned or already in progress at UCSF include efforts to determine the genetic basis of a range of common diseases: diabetes, autoimmunity, multiple sclerosis, obesity, and cancer. The main projects outlined in this proposal are cancer related, and it is proposed to house the equipment within the Cancer Center. However, the Sequenom MassArray will be part of the newly formed Consolidated Genome Core and will be available to all participating institutions and departments at UCSF and its affiliated institutions. Relevance The Federal Government, through NIH/NCI funded initiatives, has made a major investment in the genetics of human disease. The human and mouse genome projects have cost billions of dollars, but the translation of this information into tangible benefits for patients is still in its infancy. These projects will exploit the vast patient and tissue resources at UCSF in an attempt to relate disease susceptibility to the underlying genetics of the host, and is thus fits with the overall strategic aims of the NIH. [unreadable] [unreadable] [unreadable]